metastatic breast cancer

The primary objective of this study is to demonstrate equivalent pharmacokinetics (PK) in terms of area under the curve at steady state (AUCSS) between CT-P6 and the comparator, Herceptin®, in patients with metastatic breast cancer. The secondary objective is to obtain additional comparative PK data, as well as initial safety and efficacy data with CT-P6 in comparison to Herceptin® in patients with metastatic breast cancer.

CT-P6

Trastuzumab

Powder for concentrate for solution for intravenous infusion

150

The primary objective of this study is to demonstrate equivalent pharmacokinetics (PK) in terms of area under the curve at steady state (AUCSS) between CT-P6 and the comparator, Herceptin®, in patients with metastatic breast cancer.
The secondary objective is to obtain additional comparative PK data, as well as initial safety and efficacy data with CT-P6 in comparison to Herceptin® in patients with metastatic breast cancer.

Inclusion Criteria
Patients will be entered into this study only if they meet all of the following criteria:
1. Written and signed informed consent, obtained prior to starting any
protocol-specific procedures.
2. Are females over 18 years of age.
3. Have pathologically confirmed, uni-dimensionally measurable metastatic breast
cancer.
4. Have a strong Her-2 over-expression as described by a 3+ score by
immunohistochemistry (IHC) or a positive fluorescence in-situ hybridisation
(FISH) or chromogenic in-situ hybridisation (CISH) result.
5. Have target lesions outside prior radiation fields.
6. Have Eastern Cooperative Oncology Group (ECOG) performance status 0 or 1.
7. Have at least 4 weeks since last surgery or radiation therapy, with full recovery.
8. Are expected to survive for at least 6 months.
9. Are not pregnant and do not plan to become pregnant during the study.

Exclusion Criteria
Patients will NOT be entered into this study if they meet any of the following criteria:
1. Have received prior chemotherapy for metastatic breast cancer.
2. Current clinical or radiographic evidence of central nervous system (CNS)
metastases. A computerised tomography (CT) or magnetic resonance imaging
(MRI) scan of the brain is mandatory in cases of clinical suspicion of brain
metastases within 21 days of randomisation. Eligible patients must be
asymptomatic and cannot be receiving steroids.
3. Are receiving concurrent immunotherapy or hormonal therapy.
4. Have a history of congestive heart failure (CHF) of any New York Heart
Association (NYHA) criterion, or serious cardiac arrhythmia requiring treatment
(except for atrial fibrillation and/or paroxysmal supraventricular tachycardia).
5. Have an abnormal LVEF (≤50%) at baseline, as determined by either
two-dimensional echocardiogram (ECHO) or multiple-gated acquisition (MUGA)
scan. If the patient is randomised, the same method of LVEF assessment, ECHO
or MUGA, must be used throughout the study.
6. History of myocardial infarction within 6 months before randomisation.
7. Current uncontrolled hypertension (systolic blood pressure >150 mmHg and/or
diastolic blood pressure >100 mmHg), or unstable angina.
8. Have severe dyspnoea at rest due to complications of advanced malignancy or
requiring supplementary oxygen therapy.
9. Have had a prior malignancy within the last 5 years that might affect breast
cancer diagnosis or assessment.
10. Have had prior mediastinal irradiation (except internal mammary-node irradiation
for the present breast cancer).
11. Have received cumulative doses of anthracycline exceeding 360 mg/m2 of body
surface area for doxorubicin, 720 mg/m2 for epirubicin, 120 mg/m2 for
mitoxantrone, 90 mg/m2 for idarubicin, or the equivalent of 360 mg/m2 of
doxorubicin for other anthracyclines such as liposomal doxorubicin. If more than
one anthracycline has been used, then the cumulative dose must not exceed the
equivalent of 360 mg/m2 of doxorubicin.
12. Have received stem-cell support for chemotherapy.
13. Have a history of hypersensitivity to the trastuzumab or to drugs with similar
chemical structures, or to any of the excipients, or to murine proteins.
14. Have a history of severe hypersensitivity reaction to paclitaxel, or to any of the
excipients.
15. At study entry, have an absolute neutrophil count ≤1,500/L or platelet count
≤100,000/L
16. At study entry, have haemoglobin level ≤9 g/dL.
17. At study entry, have aspartate aminotransferase (AST) or alanine
aminotransferase (ALT) levels >2.5 x upper limit of normal (ULN) (>5 x ULN in
patients with liver metastases), or serum (total) bilirubin >1.5 x ULN.
18. At study entry, have a serum creatinine level >2.0 mg/dL.
19. Have any other medical or psychiatric condition that could compromise study
participation.
20. Have received treatment with any other investigational drug in the last 30 days
before study entry, or within less than five half-lives after receiving the previous
investigational drug.
21. Current known infection with human immunodeficiency virus (HIV), hepatitis B
virus (HBV) or hepatitis C virus (HCV).
22. Are pregnant or a nursing mother.
23. Have a history or suspicion of unreliability, poor cooperation or non-compliance
with medical treatment.
24. Have any concurrent disease or condition that, in the opinion of the investigator,
would make the patient unsuitable for participation in the study.
25. Have previously been enrolled in this study.